Molecular imaging of tumors and metastases using chemical exchange saturation transfer (CEST) MRI

Abstract

The two glucose analogs 2-deoxy-D-glucose (2-DG) and 2-fluoro-2-deoxy-D-glucose (FDG) are preferentially taken up by cancer cells, undergo phosphorylation and accumulate in the cells. Owing to their exchangeable protons on their hydroxyl residues they exhibit significant chemical exchange saturation transfer (CEST) effect in MRI. Here we report CEST-MRI on mice bearing orthotopic mammary tumors injected with 2-DG or FDG. The tumor exhibited an enhanced CEST effect of up to 30% that persisted for over one hour. Thus 2-DG/FDG CEST MRI can replace PET/CT or PET/MRI for cancer research in laboratory animals, but also has the potential to be used in the clinic for the detection of tumors and metastases, distinguishing between malignant and benign tumors and monitoring tumor response to therapy as well as tumors metabolism noninvasively by using MRI, without the need for radio-labeled isotopes.

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents

“…23,36,37 The herein reported results suggest that the investigated iodinated contrast media would perform better thanks to the larger chemical shift of the amide protons that limits the confounding effect of direct water saturation. 38,39 Moreover, in the case of quickly metabolized molecules such as glucose, it is necessary to maintain high concentration of the probe through a continuous infusion to avoid the disappearance of the corresponding CEST signal, while iodinated molecules do not undergo any metabolic process, thus maintaining a relatively constant concentration during the CEST-MRI acquisition.…”

“…20 Iodinated agents display a relatively large chemical shift between amide and bulk water protons, which confers favorable CEST imaging properties in comparison to molecules such as glucose and glucose analogs. [21][22][23] In addition, when compared with paramagnetic CEST agents, they require lower saturation power pulses to efficiently saturate their resonances, therefore limiting specific absorption rate issues that often may represent a bottleneck on the way of the clinical translation of CEST agents. 24,25 Herein we report a systematic characterization of the CEST properties of 4 radiographic CAs, belonging to monomeric low-osmolar agents, namely, iomeprol (Iomeron; Bracco Imaging), iohexol (Omnipaque; GE Healthcare), and ioversol (Optiray; Mallinckrodt Inc), and to dimeric isoosmolar agents, iodixanol (Visipaque; GE Healthcare), respectively Our study determines their pH-dependent chemical exchange properties in vitro to elucidate their contrast enhancement and sensitivity.…”

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging

“…However, for glucose, the main drawback was associated to its rapid metabolism once entered in the tumor cells, with consequent reduction of CEST contrast capabilities. For this reason, glucose analogs, such as 2-deoxy-glucose (2DG) and 3-oxy-methyl-gluose (3OMG) have been proposed as they showed superior contrast efficiency owing to the reduced metabolic conversion in the case of 2DG (Nasrallah et al, 2013;Rivlin et al, 2013) or to the lack of metabolic transformation in the case of 3OMG (Rivlin et al, 2014). As a consequence, such derivatives provide an improved and long-lasting CEST contrast in mice carrying xenograft tumors.…”

Current status and future role of brain PET/MRI in clinical and research settings

“…Using hybrid amyloid PET/MRI, the iron-based imaging of brain β-amyloid load could be further improved by directly relating it to actual regional β-amyloid depositions according to the established PET measure. Following the same principle, hybrid [ 18 F]FDG PET/MRI could also be employed to validate a recently introduced, radiation-free MR method to measure FDG accumulation in cancer cells [29]. This MR approach based on chemical exchange saturation transfer (CEST) is still restricted to use in small animals with high field MRI (7 T), but hybrid PET/MRI may facilitate its translation towards use in humans.…”